New opportunities for discovery through data analysis, modeling, and simulation are constantly emerging within the biological and biomedical sciences, as well as in traditional physical and social sciences. A realization of the last decade, however, is that our ability to cope with this data influx has not kept pace and that the creation of tools that allow us to process large-scale data sets judiciously is one of the central challenges of the present age. We will discuss the kinds of challenges scientists are facing, some examples of success, and some of failure.